Introduction: MANEC is a rare diagnosis and little is known on its epidemiology/prognosis/management.
Methods: Demographic/clinical-pathological/survival data of patients with a diagnosis of MANEC (2010 WHO criteria) from five European centres were retrospectively reviewed.
Results: Sixty-six patients were identified (09/8007/17); median age: 62.5 years (range 3489); male: 66.7%; ECOG-PS 0-1: 59%; primary tumours from: small/large bowel 62.1%, oesophagus/stomach 22.7%, pancreas/biliary tract 13.6%, unknown 1.5%; adult-comorbidity-evaluation (ACE)-27 score 0: 36.4%. The NE component (predominant histology in 58.1% of 43 cases where this information was available) was poorly-differentiated (PD) in 80.3%, with a median Ki-67 value of 70% (95%-Confidence-Interval (CI): 6073.6). Most frequently expressed IHC markers were: synaptophysin (87.9%), chromogranin-A (CgA) (54.5%) and CDX2 (48.5%). Histology from recurrent/metastatic sites (14 patients) was PD-NE in 71.4%. Median follow-up time was 11.5 months (mo). Of 34 (51.5%) patients with localised-stage (LA) disease, 91.2% had curative surgery (22.5% had neoadjuvant chemo-radiotherapy (CT-RT), 29% had adjuvant or peri-operative CT), 5.9% had definitive CT-RT and 2.9% had unknown management; 77.4% recurred. Fifty-four (81.8%) patients were treated for advanced-stage (adv) disease: 50% had platinum-based CT, 5.5% irinotecan-based CT, 1.8% gemcitabine, 1.8% 5-fluorouracil/leucovorin, 3.7% unknown CT regimen, 1.8% CT-RT, 1.8% RT, 24% best-supportive-care (BSC), and 9.25% unknown management. Median overall-survival (OS) for all patients was 16.2 mo (95%-CI 12.121). Median recurrence-free-survival and OS in patients with LA disease were 12.9 mo (95%-CI 6.721) and 21 mo (95%-CI 14.5735). Median progression-free-survival (PFS) and OS in patients with adv disease were 4.9 mo (95%CI 3.57.2) and 14.6 mo (95%CI 9.619.4). On univariable analysis, age <70 years and ACE-27 score 0 (vs≥1) were prognostic for better OS (both P<0.05); IHC negativity for CgA and first-line active treatment (vsBSC) were prognostic for better PFS (both P<0.05).
Conclusion: This is one of the largest series of MANEC in current literature. PD-NE is predominant in both primary tumours and recurrent/metastatic sites. Survival outcomes are poor. Curative surgery is the preferred choice for LA patients. Platinum-based CT is the most frequently offered strategy in the adv setting.
04 Dec 2017
UK and Ireland Neuroendocrine Tumour Society